Coal-Derived Humic Substances: Insight into Chemical Structure Parameters and Biomedical Properties.

An investigation was carried out on humic substances (HSs) isolated from the coal of the Kansk-Achinsk basin (Krasnoyarsk Territory, Russia). The coal HSs demonstrate the main parameters of molecular structure inherent to this class of natural compounds. An assessment was performed for the chemical, microbiological, and pharmacological safety parameters, as well as the biological efficacy. The HS sample meets the safety requirements in microbiological purity, toxic metals content (lead, cadmium, mercury, arsenic), and radionuclides. The presence of 11 essential elements was determined. The absence of general, systemic toxicity, cytotoxicity, and allergenic properties was demonstrated. The coal HS sample was classified as a Class V hazard (low danger substances). High antioxidant and antiradical activities and immunotropic and cytoprotective properties were identified. The ability of the HS to inhibit hydroxyl radicals and superoxide anion radicals was revealed. Pronounced actoprotective and nootropic activities were also demonstrated in vivo. Intragastric administration of the HS sample resulted in the improvement of physical parameters in mice as assessed by the "swim exhaustion" test. Furthermore, intragastric administration in mice with cholinergic dysfunction led to a higher ability of animals with scopolamine-induced amnesia to form conditioned reflexes. These findings suggest that the studied HS sample is a safe and effective natural substance, making it suitable for use as a dietary bioactive supplement.

Peptide ligands on the PEGylated nanoparticle surface and human serum composition are key factors for the interaction between immune cells and nanoparticles.

The architecture of a nanoparticles' surface formed due to a modification with a ligand and protein corona formation in biofluids is critical for interactions with cells in vivo. Here we studied interactions of immune cells with magnetic nanoparticles (MNPs) covalently modified with polyethylene glycol (PEG) and their counterparts conjugated with peptides: a pH (low) insertion peptide (pHLIP) and cycloRGD as a targeting ligand in human serum. The conjugation of MNPs-PEG with pHLIP, but not with cycloRGD, enhanced the association of these particles with mononuclear phagocytic cells in vitro and in vivo. We did not find a clear difference in protein corona composition between the pHLIP-modified and parental PEGylated nanoparticles. Analysis of the effect of autologous human serum on MNP uptake by monocytes showed that the efficiency of endocytosis varies among healthy donors and depends on intrinsic properties of serum. Nevertheless, using classic blood, coagulation, biochemical tests, and anti-PEG IgG serum level, we failed to identify the cause of the observed interdonor variation. These individual differences should be taken into consideration during testing of nanotherapeutics.

UMAOH Calcium Phosphate Coatings Designed for Drug Delivery: Vancomycin, 5-Fluorouracil, Interferon α-2b Case.

Drug delivery systems based on calcium phosphate (CaP) coatings have been recently recognized as beneficial drug delivery systems in complex cases of bone diseases for admission of drugs in the localized area, simultaneously inducing osteoinduction because of the bioavailable Ca and P ions. However, micro-arc oxidation (MAO) deposition of CaP does not allow for the formation of a coating with sufficient interconnected porosity for drug delivery purposes. Here, we report on the method to deposit CaP-based coatings using a new hybrid ultrasound-assisted MAO (UMAOH) method for deposition of coatings for drug delivery that could carry various types of drugs, such as cytostatic, antibacterial, or immunomodulatory compositions. Application of UMAOH resulted in coatings with an Ra roughness equal to 3.5 µm, a thickness of 50-55 µm, and a combination of high values of internal and surface porosity, 39 and 28%, respectively. The coating is represented by the monetite phase that is distributed in the matrix of amorphous CaP. Optimal conditions of coating deposition have been determined and used for drug delivery by impregnation with Vancomycin, 5-Fluorouracil, and Interferon-α-2b. Cytotoxicity and antimicrobial activity of the manufactured drug-carrying coatings have been studied using the three different cell lines and methicillin-resistant S. aureus.

Is there a real need for sputum culture for community-acquired pneumonia diagnostics? Results from a retrospective study in Russia.

OBJECTIVES: The mortality rate associated with community-acquired pneumonia is still considered high as it occupies a leading position among all infectious diseases. The primary purpose of this study is to evaluate the implementation of the respiratory bacterial culture sampling in the clinical practice of the Russian Federation's therapeutic departments and its impact on inpatient care. METHODS: The study included 1,344 patients with community-acquired pneumonia. The analysis of the obtained data was performed using the statistical software package SPSS 23.0 (IBM SPSS Statistics). The description of quantitative indicators was carried out with an indication of the median (25; 75 percentile). Qualitative with an indication of the absolute and relative frequencies n (%). RESULTS: It was noted that a third of the sample did not pass through the first stage (bacterioscopy). We noticed the predominance of oropharyngeal flora in the results. The sputum collection was carried out on average 3 (1; 5) days after the start of hospitalization, while antibiotic therapy was prescribed to all patients on the first day, the results of the bacteriological study were ready on average 6 (4; 8th) calendar days after hospitalization, while in 20 (1.5%) cases, the patient was already discharged. Due to the inefficiency of the starting regimen, antimicrobial agents have changed in 84 (6.3%) patients and averaged 5.5 (4.0; 10.0) days from the start of hospitalization. CONCLUSIONS: The violation of the technique and the time of sputum collection resulted in a reduction in the method's value.

[Searching for additional markers of impaired iron metabolism in diabetes mellitus].

BACKGROUND: It is known that metabolic disorders in diabetes mellitus have a regulating effect on ferrokinetics, and therefore diabetes mellitus is often accompanied by various disorders of iron metabolism, both anemia and secondary iron overload. The main problem is timely and accurate differential diagnosis between anemia of chronic diseases and iron deficiency anemia. It is necessary to establish reliable laboratory markers of anemia of chronic diseases in order to solve this problem, as well as to understand what metabolic disorders can lead to the occurrence and aggravate the course of this type of anemia. AIMS: To study the frequency of occurrence of violations of ferrokinetics in patients with diabetes mellitus, as well as to establish clinical and biochemical correlations that are significant in the differential diagnosis of various disorders of iron metabolism: iron deficiency anemia, anemia of chronic diseases and dysmetabolic iron overload syndrome in diabetes mellitus. MATERIALS AND METHODS: The research design a single-stage observational single-center research. The research was conducted on the basis of the endocrinological clinic of the Federal State Budgetary Educational Institution of Higher Education Siberian State Medical University in Tomsk. The research included 76 patients with type 1 and type 2 diabetes mellitus. We conducted an assessment of all patients as follows: anthropometric data assessment; glycated hemoglobin study; creatinine level study with the calculation of glomerular filtration rate (GFR) using the CKD-EPI formula. We also evaluated the number of erythrocytes, reticulocytes, the hemoglobin concentration, haematocrit level and biochemical parameters of iron metabolism: serum iron and ferritin concentrations; the concentration of hepsidin and non-specific markers of inflammation: erythrocyte sedimentation rate (ESR) and highly sensitive C-reactive protein (CRP). RESULTS: 20 people (26.3%) of the 76 patients included in the study, had type 1 diabetes mellitus and 56 people (73.3%) had type 2 diabetes mellitus. The parameters of ferrokinetics did not significantly differ in patients with type 1 and type 2 diabetes mellitus, while in the group of patients with 20 patients (26.3%) from the 76 ones included into the research had type 1 diabetes mellitus and 56 (73.3%) from them had type 2 diabetes mellitus. The parameters of ferrokinetics did not significantly differ in patients with type 1 and type 2 diabetes mellitus, while in the group of patients with type 2 diabetes mellitus, the levels of CRP (p=0.034) and blood leukocytes (p=0.020) were significantly higher than in patients with type 1 diabetes mellitus. Both in the main group of patients with impaired carbohydrate metabolism, and in patients with type 2 diabetes mellitus, anemia of chronic diseases prevailed in the structure of the anemia syndrome. After dividing the main group of patients into groups by type of anemia syndrome: absence of anemia, anemia of chronic diseases and iron deficiency anemia, a comparative analysis of the average values of markers of inflammation and the level of hepsidin in these groups was performed. It was found that in patients with anemia of chronic diseases, the level of hepsidin is significantly higher than in patients without anemic syndrome (p=0.033). Paired correlation analysis showed a positive correlation of ESR with microalbuminuria (r=0.515; P<0.0001), creatinine level (r=0.467; P<0.0001) and negative — with GFR (r= -0.436; P<0.0001) and iron in serum (r=-0.276; p=0.017). As the result of ROC analysis the most informative in the diagnosis of anemia of chronic disease were: ferritin — sensitivity 78%, specificity 52% with a diagnostic threshold of 75.5 ng/ml (area under the curve 0,695; p=0.006); ESR — sensitivity 67%, specificity 64% with a diagnostic threshold of 15.5 mm/HR (area under the curve of 0.750 in; p=0.040) and the CRP — sensitivity 67%, specificity 64% with a diagnostic threshold of 5.2 ng/ml (area under the curve 0,646; р<0.0001). CONCLUSION: Thus, the studied markers of inflammation — ESR and CRP, as well as hepsidin in combination with the classic diagnostic parameter — ferritin, demonstrated high value in the diagnosis of anemia of chronic diseases and can be included in the modified algorithm for differential diagnosis of anemia syndrome in patients with diabetes mellitus.